immature oocytes to radiation-induced killing (the majority are destroyed by 0.5 Gy; Oakberg and Clark 1964) in contrast to those of human and rhesus monkey immature oocytes, for which the dose required is at least 100 times higher (Baker 1971) and (2) the observations that no mutations were recovered from oocytes sampled 7 weeks after irradiation in contrast to the situation with mature and maturing oocytes (Russell 1965). In view of this uncertainty and in order not to underestimate the risk, the committee has used the assumption that the rate estimated for males will also be applicable to females.

Details of the data used are summarized in Tables 4-3A to 4-3C and are from experiments involving acute X-irradiation or from high-dose fractionated X-irradiation (usually two fractions separated by 24 h) appropriately normalized to acute X-irradiation conditions (see Table 4-3A, footnote d; and Table 4-3B, footnotes a and b) to permit easy comparisons. Table 4-3A shows that the average rate of induced mutations is highest at the original seven specific loci (3.03 × 10−5 per locus per gray) and is about one-third of the above at the six loci used in the experiments of Lyon and Morris (1969; i.e., 0.78 × 10−5 per locus per gray; one locus, a, is common to both sets). For various sets of biochemical loci at which null mutations have been scored, the estimates vary over a range from 0.24 × 10−5 to 1.64 × 10−5 per locus per gray. The average rate for dominant visible mutations is within the above range. The unweighted average of the induced mutation rates is 1.09 × 10−5 per locus per gray for acute irradiation. The use of this rate for DD calculations, however, is somewhat problematic since (1) there is overlap of one or more loci in different data sets; (2) in some studies (see footnote e, Table 4-3A), all of the loci involved could not be ascertained; and (3) there is no simple way of taking into account the interlocus variation and sampling variance of induced rates from the derived average estimate of 1.09 × 10−5 per locus per gray.

TABLE 4-3A Database for Calculating Rates of Induced Mutations in Mice

System

No. of Loci

Average Rate/Locus/Gy (× 105)

Reference

1. The 7-locus system (Lyon and others 1964) (3 and 6 Gy; acute X- or γ-irradiation or 3 + 3 Gy, 24 h interval)

7a

3.03

Phillips (1961);

Russell (1965, 1968);

Lyon and others (1972);

Cattanach and Rasberry (1994);

Pretsch and others (1994)

2. The 6-locus system (Lyon and others 1964) (6 Gy; acute X-irradiation)

6b

0.78

Lyon and Morris (1969)

3. Biochemical loci (recessive, null enzyme) (3 + 3 Gy, 24 h interval; X-rays)

12c

0.70d

Charles and Pretsch (1986);

Pretsch and others (1994)

4. Biochemical loci (recessive, null enzyme) (3 Gy, 3 + 3 Gy, 24 h interval and 6 Gy; X-rays)

32e

32

32

1.64

0.67d

0.24

Unpublished data of S.E. Lewis, cited in Neel and Lewis (1990)

5. Biochemical loci (recessive, null enzyme) (3 + 3 Gy, 24 h interval; X-rays)

4f

1.24d

Unpublished data of J. Peters, cited in Neel and Lewis (1990)

6. Dominant visibles (Sl, W, Sp and T)g (X rays)

4

0.44

See Table 4-3B

Unweighted average: 8.74/8 = 1.09 × 10−5 per locus per gray

NOTE: Data are from experiments involving irradiation of males (stem cell spermatogonia) and all rates are normalized to single acute X-irradiation conditions.

aa: non-agouti; b: brown; c: chinchilla; d: dilute; p: pink-eyed dilution; s: piebald; se: short ear; in the work of Pretsch and others (1994), with some strains, mutations at four or five of these loci were scored.

ba: non-agouti; bp: brachypodism; fz: fuzzy; ln: leaden; pa: pallid; pe: pearl.

cLdh1, Tpi, Gpi1, Pgk, G6pd1, G6pd2, Pk, Gr, Mod1, Pgam, Gapdh, Ldr.

dNormalized assuming additivity of the effect of dose fractionation.

eAcy1, Car2, G6pd1, Ggc, Es1, Es3, G6pd1, Gpi1, Hba, Hbb, Idh1, Ldh1, Ldh2, Mod1, Mod2, Np1, Pep2, Pep3, Pep7, Pgm1, Pgm2, Pgm3, Pk3, Trf (the identity of the other 8 loci could not be ascertained).

fHba, Hbb, Es3, Gpi1.

gSl: steel; W: dominant spotting; Sp: splotch; T: brachyury.



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